Activity and phylogenetics of the broadly occurring family of microbial nep1-like proteins

Necrosis-and ethylene-inducing peptide 1 (Nep1)-like proteins (NLP) have an extremely broad taxonomic distribution; they occur in bacteria, fungi, and oomycetes. NLPs come in two forms, those that are cytotoxic to eudicot plants and those that are noncytotoxic. Cytotoxic NLPs bind to glycosyl inositol phosphoryl ceramide (GIPC) sphingolipids that are abundant in the outer leaflet of plant plasma membranes. Binding allows the NLP to become cytolytic in eudicots but not monocots. The function of noncytotoxic NLPs remains enigmatic, but the expansion of NLP genes in oomycete genomes suggests they are important. Several plant species have evolved the capacity to recognize NLPs as molecular patterns and trigger plant immunity, e.g., Arabidopsis thaliana detects nlp peptides via the receptor-like protein RLP23. In this review, we provide a historical perspective from discovery to understanding of molecular mechanisms and describe the latest developments in the NLP field to shed light on these fascinating microbial proteins.